Abstract
A chemo-enzymatic synthesis of 9-(β-d -arabinofuranosyl)-2-fluoroadenine
(Fludarabine) and 9-(β-d -arabinofuranosyl)-2-amino-6-methoxypurine
(Nelarabine) using α-d -arabinofuranose 1-phosphate
as a universal substrate and recombinant E.
coli purine nucleoside phosphorylase (PNP) as a biocatalyst
is described. MacDonald’s method was employed for the synthesis
of α-d -arabinofuranose 1-phosphate,
which was prepared as a mixture with β-d -arabinopyranose
1-phosphate, starting from peracyl derivatives of d -arabinose
of different isomeric (anomeric) composition. It was found that
the mixed phosphates can be successfully used in the reaction with
purine base catalyzed by PNP pointing to the inertia of β-d -arabinopyranose 1-phosphate in regard
to PNP. Reaction of 2-fluoroadenine and α-d -arabinofuranose
1-phosphate is shifted towards the formation of Fludarabine, whereas
the reaction of 2-amino-6-methoxypurine reached equilibrium at a
ca. equimolar ratio of the base and Nelarabine. Recombinant E. coli uridine phosphorylase catalyzed
the synthesis of 1-(β-d -arabinofuranosyl)thymine (ara-T)
from thymine and α-d -arabinofuranose
1-phosphate.
Key words
α-d -arabinofuranose 1-phosphate - recombinant E.coli nucleoside phosphorylases - purine nucleosides - ara-T
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